key: cord-0754685-sl1o9r7b
authors: Wang, Fei; Huang, Liqian; Zhang, Peng; Si, Yang; Yu, Jianyong; Ding, Bin
title: Antibacterial N-halamine fibrous materials
date: 2020-09-12
journal: nan
DOI: 10.1016/j.coco.2020.100487
sha: 73fedee6be34a1ac420b8bd4ad820953875854d0
doc_id: 754685
cord_uid: sl1o9r7b

Pathogenic microbial contamination poses serious threats to human healthcare and economies worldwide, which instigates the booming development of challenging antibacterial materials. N-halamine fibrous materials (NFMs), as an important part of antibacterial materials, featuring structural continuity, good pore connectivity, rapid sterilization, rechargeable bactericidal activity, and safety to humans and environment, have received significant research attention. This review aims to present a systematic discussion of the recent advances in N-halamine antibacterial fibrous materials. We firstly introduce the chemical structures and properties of N-halamine materials. Subsequently, the developed NFMs can be categorized based on their fabrication strategies, including surface modification and one-step spinning. Then some representative applications of these fibrous materials are highlighted. Finally, challenges and future research directions of the materials are discussed in the hope of giving suggestions for the following studies.

with >640000 deaths worldwide and increasing, which caused incalculable misery and economical loss [1, 2] . To cut off the pathogen spreading by the proliferation of microbials, the commonly used strategies dealing with these challenges are the addition of disinfectants to the contact surfaces [3] [4] [5] . Despite the effectiveness of the developed disinfectants, such as metallic silver [6, 7] , quaternary ammonium salt [8, 9] , chitosan [10] , and peptide [11] , they still experienced the problem of drastic antibacterial performance decline induced by irreversible depletion of disinfectants.

Alternatively, N-halamines have attracted increasing attention owing to its rapid inactivation, renewable biocidal activity, broad-spectrum antibacterial, long-term stability, and safety to humans and environments [12] .

N-halamine was first proposed as halogen derivatives of nitrogen by Gmelin in their coverage of inorganic chemistry in 1927 [13] . Later in 1970, Kovacic et al. [14] presented an overall discussion of the chemistry of N-bromo and N-chloro derivatives of ammonia and alkylamines. Then Worley and co-workers were devoted in the synthesis of novel N-halamine compounds in the late 1980s [15] [16] [17] . Nowadays, N-halamines can be more precisely defined as inorganic or organic compounds containing one or more nitrogen-halogen covalent bonds that obtained by J o u r n a l P r e -p r o o f halogenation of N-H groups, the halogen is chlorine, bromine, or iodine. In terms of the antibacterial function, the N-X covalent bonds can hydrolyze in the presence of water and be reduced to N-H covalent bonds, the released oxidative halogens would directly react with the vital bacterial cell constituents affecting metabolism and viability [18, 19] . Once oxidative halogens are consumed, as a reverse process, the N-H groups can be facilely recharged by exposure to dilute household bleach or halogen-releasing agents, bringing renewable antibacterial activity to N-halamines.

With the remarkable progress of diverse N-halamine compounds, considerable attention has been paid to developing N-halamine materials in various forms (fibers, nanoparticles, beads, films, etc.) for creating better antibacterial activity [20] [21] [22] [23] .

Among them, NFMs are found to be highly attractive due to their advantages like exceptional structural continuity, good pore connectivity, fine flexibility, and self-supporting capability, which show great potentials in a wide range of applications.

In this following context, we discuss state-of-the-art of studies on the design, fabrication, and functional applications of NFMs. Firstly, we briefly state the molecular structures and antibacterial behavior of N-halamine materials, and introduce their various morphologies. Then we emphasize on recent advances regarding NFMs based on the fabrication strategies of surface modification and one-step spinning. Subsequently, we comprehensively highlight the functional applications of NFMs in varieties of fields, involving bioprotective clothing, water disinfection, air purification, and biomedicine. Finally, a summary and outlook for J o u r n a l P r e -p r o o f next-generation N-halamine antibacterial fibrous materials is provided.

In drastic contrast to traditional halogen-based disinfectants, the N-halamines are more diverse in their molecular structures, which could be classified into three types based on the different halogenation groups, i.e., amine N-halamines, amide N-halamines, and imide N-halamines (Fig. 1a) . The bactericidal activities of these structures in aqueous solutions are found to be the order of imide N-halamines, amide N-halamines, and amine N-halamines, which is ascribed to progressively smaller dissociation constant of the N-halamines [24] . On the contrary, their stability follows a totally opposite tendency, the imide N-halamines are the least stable structure that can quickly release active halogens and be reverted to the precursor [25] . It means that imide N-halamines could be used for rapid inactivation, while for durable antibacterial applications, amine N-halamines will be the best choice. Moreover, the stability and durability of N-halamines is bound up with the existence or not of an α-hydrogen, a dehydrohalogenation reaction occurs under ultraviolet (UV) radiation or heat if α-hydrogen exists (Fig. 1b) . Dehydrohalogenation of N-halamines with α-hydrogen. Reprinted from Ref. [25] .

Copyright 2013 American Chemical Society.

N-halmines could also be divided into small molecular N-halamines and polymeric N-halamines. In the early years of N-halamines studies, numerous small molecular N-halamines had sprung up due to their better stability than existing disinfectants, including inorganic and organic N-halamines [15] [16] [17] [26] [27] [28] [29] [30] [31] . The typical inorganic N-halamines such as NH 2 Cl, NHCl 2 , and NCl 3 , were usually synthesized by substitution reaction of ammonia with hypochlorous acid or chlorine gas, which were found to be highly attractive in the applications of water disinfection [13] . In terms of organic small molecular N-halamines, some typical N-halamines can be subdivided according to the chemical structure of the molecule. The five-membered heterocyclic N-halamines like hydantoin-containing N-halamines ( Fig.   2a ), imidazolidinone-containing N-halamines (Fig. 2b) , oxazolidinone-containing N-halamines (Fig. 2c) , and succinimide-containing N-halamines (Fig. 2d) . The triazine N-halamines, such as melamine-containing N-halamines (Fig. 2e) , cyanuric acid-containing N-halamines (Fig. 2f) , cyanuric chloride-containing N-halamines (Fig.   2g ), others like acrylamide-containing N-halamines (Fig. 2h) , 4-piperidinol-containing N-halamines (Fig. 2i) . Despite the considerable bactericidal activity and long-term stability in aqueous solution, the major problems associated with small molecular N-halamine compounds were the solubility in water and the required toxicity testing before commercial use [32, 33] . Moreover, the common powder form of the J o u r n a l P r e -p r o o f compounds and the inability to directly incorporate into the substrate materials, putting limitations on their practical applications. To cope with these challenges, small molecular N-halamines with active groups (e.g., hydroxyl group, epoxy group, and silanol group) have attracted great attention because they could be recognized and covalently loaded on substrates by reacting with the functional groups, which provide more possibilities for the development of N-halamine materials [24, 34, 35] . Based on the research findings of small molecular N-halamines, polymeric N-halamines are rapidly emerging, which may be deemed to the derivatization of polymers with halamine groups. Benefitting from the advantages of insolubility in water, ultralow leaching amounts of free active halogens, easy to modification, good J o u r n a l P r e -p r o o f processability, and recycling properties, the polymeric N-halamines have become another powerful and effective way to synthesize novel N-halamine materials for different application requirements [36, 37] . Generally speaking, four strategies are used to fabricate polymeric N-halamines. The first route is to graft the small molecular N-halamines onto polymer backbones by chemical reaction of functional groups as exhibited in Fig. 3a -d, the small molecular N-halamines are grafted onto nylon [38] , polystyrene [39] , polysiloxane [40] , and polyhydroxybutyrate (PHB) [41] .

Secondly, the small molecular N-halamines can graft onto polymer by graft polymerization. For example, Fig. 3e -g show the polymeric N-halamines that are fabricated by graft polymerization of N-halamine monomer with polypropylene (PP) [42] , cellulose [43] , and poly(ethylene terephthalate) (PET) [44] . The third strategy is the polymerization of N-halamine monomer by reacting with themselves or other monomers ( Fig. 3h-i) [45, 46] . The last approach is blending or coating N-halamine compounds to the main polymers, which is not covalently incorporated the N-halamine groups into polymers [47, 48] .

J o u r n a l P r e -p r o o f poly(m-phenyleneisophthalamide). Reprinted from Ref. [46] . Copyright 2004 American Chemical Society.

Although N-halamines materials have received considerable attention in both industrial and academic circles, their antibacterial behavior still remains controversies.

To date, three possible antibacterial pathways have been proposed, that is, contact killing, release killing, and transfer killing (Fig. 4) . The first mode kills bacteria through delivering active halogens from N-halamines to the bacteria directly without releasing active halogen into solution, whereas the second is the dissociation of positive halogen ions from N-halamines to solution with the following killing. Apart from these, a third mode has been proposed by some researchers, transfer killing, which is a way of achieving inactivation through transferring the positive halogens from N-halamine materials to medium. with antibacterial properties after being exposed to household bleach. It was found that the release rate of N-halamine precursor was low even conducting with vigorous agitation, suggesting that the materials inactivate bacteria via contact killing instead of release killing. Thereafter, Bai et al. [50] investigated the antibacterial behavior of the as-prepared N-Br bond-containing N-halamine nanofibers using inhibition zone test, the appearance of the distinct aseptic ring around the samples validated the release killing mode. Then they tested release rate of active bromine dissociated from the N-halamine nanofibers under different conditions. Above 80% active bromine content maintained under a dry condition, while only 6% active bromine left when exposing into bacteria or water condition, implying that the materials inactivate bacteria by release killing mode.

The transfer killing mode was confirmed by Ahmed's report [51] , the bacteria were cultured in fresh broth and in broth that are pre-treated by exposure to chlorinated polymer, respectively. The results showed that the bacteria failed to grow in the pre-treated medium, which was ascribed to the changes from the halogen exchange between the amide groups in protein and the polymer. More interestingly, they proposed that the bactericidal mode could not be explained alone but a combination of these modes operating simultaneously. Bai et al. [52] studied the antibacterial J o u r n a l P r e -p r o o f behavior of the N-halamine containing poly(methyl methacrylate) (PMMA) fibers by referring research methods of Ahmed. The freeze-dried bacterial cells in the absence of liquid environment were used to verify the contact killing mode. An inhibition zone testing method was conducted to identify the release killing of the materials, afterward a dialysis test was further carried out to determine the release action of the fibers. As a result, the antibacterial mode of the swatches was attributed to the combination of these two modes. Besides, Chen et al. [53] also believed that combination of these modes would be a more reasonable explanation of the antibacterial activities. Compared with the sodium hypochlorite (NaClO) solution, the inactivation properties of N-halamine modified cotton fabrics was much higher than that of the NaClO solution, indicating that the release killing mode alone may not be enough to ensure efficient bactericidal function. Overall, the N-halamines containing relatively stable N-X bonds tend to follow the contact killing mode, and those containing less stable halamine functional groups are likely to kill bacteria by release killing. The liquid environment and media that containing N-H groups also play decisive roles in the bactericidal behavior of the materials.

The morphology of N-halamine materials plays a decisive role in their antibacterial activities and applications. So far, researchers have fabricated various N-halamine materials with controllable morphologies, mainly including sphere-shaped, film-shaped, and fiber-shaped. For sphere-shaped N-halamine materials, varieties of beads, microspheres, and nanoparticles have been synthesized [54] [55] [56] [57] [58] [59] [60] [61] . The spherical J o u r n a l P r e -p r o o f morphology endowed the materials with higher specific surface area and more active sites than that of the other two morphologies, and it can be easily filled in various molds or be loaded onto other carriers for different application scenarios. Sun and co-workers [54] have firstly prepared N-halamine beads through suspension copolymerization of styrene and two small N-halamine molecular compound, another is to prepare materials by one-step spinning. A detailed description of these two methods will be presented as follows. J o u r n a l P r e -p r o o f

The chemical surface modification method can effectively incorporate the N-halamine moieties into fibrous substrates via covalently linkage, achieving strong chemical attachment between them. Generally, it is usually required that the fibrous substrates are impregnated in N-halamine-containing modification solutions to make a sufficient loading, and they can serve as a reactant to participate in the chemical reaction. Based on this, the chemical surface modification can be sorted by the types of chemical reaction. One is surface modification by small molecules, which means that N-halamine moieties react with active groups of fibrous substrates; the other is the J o u r n a l P r e -p r o o f graft polymerization of N-halamine monomers on fibrous materials.

Surface modification by small molecules is an effective and facile method for fabrication of NFMs, accounting for primary routes to connect N-halamines and substrates. It is worth mentioning that the small molecular N-halamines used for modification should contain active groups (such as hydroxyl and epoxide ring) which can incorporate onto fibrous materials through two pathways: react with fibers directly or modify materials through other chemicals. In the former case, Ma et al. [89] described a method of controlled hydrolysis of cyanuric chloride to prepare N-halamine precursors, and attached the precursors onto cotton fabrics through nucleophilic substitution using a typical pad-dry-cure process (Fig. 6a ). As exhibited in Fig. 6b , the chlorine content of modified fabric is 0.35 wt% after being exposed to In addition to the N-halamines that could be bonded to the fibrous substrates directly, many other substrates and N-halamines are not able to react with each other, a medium which serves as a bridge between N-halamines and fibrous materials is often required. Crosslinking agents, like 1,2,3,4-butanetetracarboxylic acid (BTCA) [91] [92] [93] [94] [95] [96] [97] , dimethylol-5,5-dimethylhydantoin (DMDMH) [71, 98, 99] , and citric acid [100] , have been widely applied to react with N-halamines and fibers for the fabrication of NFMs due to their excellent chemical reactivity. For example, Li et al. 

Graft polymerization has become another effective and powerful way for fabricating NFMs [18, 102] . Incorporating the N-halamine moieties onto fibrous materials through Subsequently, these two kinds of monomers could be grafted on cellulose fiber to 7a ) and

cellulose-graft-polyDMABn (C-g-PDMABn) (Fig. 7b) , respectively. Likewise, the two monomers could be grafted on cellulose fibers simultaneously to fabricate cellulose-cograft-polyAEODMABn (C-g-PAEDM) (Fig. 7c ). As presented in Fig. 7d-g, more intact bacteria were found on fiber surface of C-g-PDMABn after

contacting with E. coli, and the bacterial debris was observed on C-g-PAEDM, which corresponded to their different kinetics of antibacterial activity. That is to say, the N-halamine cellulose fiber exhibited rapid inactivation rate but weak absorption capacity, whereas QAs-functionalized cellulose fibers could quickly absorb bacteria without immediately killing them. Benefiting from the synergistic effect of these two mechanisms, the resulting bi-functional cellulose fibers showed a novel biocidal process and performed excellent antibacterial properties against both E. coli and S.

J o u r n a l P r e -p r o o f aureus (Fig. 7h-i) . Reprinted from Ref. [107] . Copyright 2014 Wiley.

In contrast to the traditional graft polymerization initiated by initiator, electron beam irradiation method, combining the rapid free radicals generation, continuous treatment process, and energy-saving property, has been applied to modify different kinds of surfaces [108, 109] . Ren et al. [79] synthesized the N-halamine compound, 

As a versatile and available modification method, surface coating is a facile solution treatment process that is able to be applied to various substrates, which involves dip coating and blade coating [110, 111] . In a typical dip coating procedure, precursor L-ascorbic acid. After being exposed to household bleach, the electrical conductivity of the cotton/rGO-PSPH-Cl was capable of monitoring their antibacterial activity according to the proportional relationship between electrical conductivity and chlorine content of the samples (Fig. 8a) . The cotton/rGO-PSPH-Cl samples achieved better biocidal efficacy than that of cotton/GO-PSPH, which could inactivate 100% of E.

coli and S. aureus within 5 min of contact (Fig. 8b) .

Layer-by-layer (LbL) assembly has proven to be markedly powerful method for coating fibrous substrates with N-halamine compound layers (usually polyelectrolytes) by dip coating [113, 114] . Generally, LbL assembly process is performed by manually immersing the fibrous substrates into solutions that containing oppositely charged chemicals alternately, followed by washing steps to eliminate unbound components [115] . The versatility, simplicity, and feasibility that LbL assembly renders make it widely used for modification of fibrous materials. Liu et al. [82] synthesized two polymeric precursors consisting of a cationic homopolymer poly((3-acrylamidopropyl) trimethylammonium chloride) (CHP) as well as an anionic homopolymer J o u r n a l P r e -p r o o f poly(2-acrylamido-2-methylpropanesulfonic acid sodium salt) (AHP), followed by coating them onto cotton fabrics using LbL assembly (Fig. 8c) . It could be clearly seen that a uniform coating layer wrapped around the cotton fiber surface when compared with the smooth surface of pristine cotton fibers (Fig. 8d-e) . By exposing to household bleach, more than 50% of the original active chlorine remained in 30 days, and the lost oxidative chlorine could regain after rechlorination (Fig. 8f) . The Reprinted from Ref. [82] . Copyright 2015 Royal Society of Chemistry.

Despite the versatility and effectiveness of dip coating, it still suffers from the drawbacks like uncontrollable modification layer and tedious process. Alternatively, blade coating has been found to be highly attractive in the modification of fibrous materials owing to its advantages of precise loading amount, durable coating layer, and good scale-up potentials [116] . As a typical example, the polymeric N-halamine precursors grafted mesoporous particles were attached onto the cotton fabric by blade coating [83] . The chlorinated samples rendered good antibacterial efficacy, which could achieve 100% and 99.99% reduction towards S. aureus and E. coli within 10 and 30 min, respectively. Moreover, the resultant cotton fabric exhibited red blood cell cohesion and better platelet adhesion, showing great potentials in the fields of biomedical applications.

Supercritical impregnation, as one of the recently developed supercritical fluid technology, has been found to be extensively appealing in surface modification of fibrous materials, owing to its environmentally friendly modification process and wide applicability, especially for inert substrates like PP fibers [40, 87] , polyethylene (PE) fibers [117] , and PET fibers [88] . In view of the integrated merits of nontoxicity, super penetration ability, and limited solubility (only dissolve small molecules), carbon dioxide (CO 2 ) is usually selected as the solvent for supercritical impregnation J o u r n a l P r e -p r o o f to deliver the N-halamine groups to substrates. More interestingly, it is feasible to manipulate the modification thickness and depth by optimizing the operation pressure, temperature, and time. Chen et al. [88] fabricated a CO 2 -philic quaternary ammonium (quat)/N-chloramine polysiloxane modified PET fibers using supercritical CO 2 impregnation (Fig. 9a) . The synthesized quat/N-chloramine polysiloxane precursors and PET fabrics were separately put in lower and upper chambers to avoid direct contact. By regulating the temperature and pressure of supercritical system, the precursors were interpenetrated into PET fibers in a controlled manner for optimal antibacterial properties. Fig. 9b demonstrated the synergistic effect of the quat/N-chloramine polysiloxane, that is, the N-halamine groups inactivate the bacteria by contact killing, and the positively charged QAs was able to attract negatively charged bacteria to promote the biocidal process. As shown in Fig. 9c and 9d, the surface of pristine PET fiber was relatively smooth while the modified PET fiber was found to be uneven and rough, which was ascribed to the existence of the coating layer. The modified PET swatches showed good durability and regeneration of chlorine against cyclic washing, and exhibited 7 logs reduction of bacteria within 10 min of contact (Fig. 9e ). Reprinted from Ref. [88] . Copyright 2017 American Chemical Society.

Studies on surface modification methods exhibit their effectiveness and operability for fabricating NFMs; however, they still suffer from some limitations such as unstable modification layers, inevitable leaching out of the N-halamine compounds, and ease of destroying original structure. Considerable efforts have been directed toward constructing NFMs by one-step fabrication process using one-step spinning, which was generally performed by spinning N-halamine polymers directly or blending N-halamine compounds in spinning precursors. Herein, we will introduce some common spinning methods for fabrication of NFMs as follows.

J o u r n a l P r e -p r o o f

As a typical technique for fabricating nanofibers, electrospinning technique has lately gained great attention for preparing antibacterial NFMs. Electrospun nanofibrous materials, combining their fascinating features of extremely fine fiber diameter, large surface area, and excellent pore connectivity, can not only endow the fibers with more active sites to incorporate functional moieties but also facilitate their contact with bacteria. The NFMs constructed by one-step electrospinning mainly comprise two types. One is blending N-halamine compounds which serve as antibacterial additives with other spinnable polymers, such as PAN [49, 118] , cellulose acetate [119] [120] [121] , nylon-6 [122] , polyurethane [48] , or PMMA [52] . The other is employing the spinnable polymeric N-halamine to fabricate electrospun fibrous materials directly [123] [124] [125] [126] [127] . In the first case, Bai et al. [52] firstly selected two N-halamine compounds, 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) and

1,3-dibromo-5,5-dimethylhydantoin (DBDMH), as the model N-halamines.

Subsequently, blending DCDMH and/or DBDMH with synthesized PMMA to prepare the precursor solution and spun it into antibacterial fibrous materials by electrospinning (Fig. 10a) . The bactericidal experiments were assessed using the plate counting. It was seen that the control plate exhibited significant bacterial growth with dense colonies, whereas no survival bacteria was observed in PMMA-DCDMH and PMMA-DBDMH plates, implying that the antibacterial activities of the N-halamine fibrous membranes come from N-halamines rather than PMMA (Fig. 10b) .

Accordingly, the survival of the bacteria is less than 0.4 after bactericidal assays of the J o u r n a l P r e -p r o o f nanofibers, indicating excellent antibacterial efficacy. (Fig. 11a) . The resulting N-halamine/silica nanofibrous membranes (NSNMs) exhibited smooth fiber surface with uniform diameter of 510 ± 83 nm (Fig. 11b) . Compared with the control membranes, the chlorinated NSNMs J o u r n a l P r e -p r o o f 32 completely killed E. coli within 3 min according to the bacterial culture plates and the morphology changes of the bacteria (Fig. 11c) . Copyright 2018 American Chemical Society.

Sea-island spinning that produces bicomponent fibers whereby many islands fibrils of one polymer are dispersed in a sea matrix of another polymer, has dramatically accelerated the development of scientific studies on the fabrication of ultrafine fibers [128] . As for the spinning process, two incompatible polymers are melt-blended together to form fibers in an islands-in-sea morphology after the process of preheating, melting extrusion, and drawing, then the sea matrix is usually removed later to leave the island fibers [129, 130] . The sea-island spinning has attracted increasing attention J o u r n a l P r e -p r o o f due to its extensive raw materials, controllable fiber morphologies, and flexible operation. Badrossamay et al. [131] utilized the synthesized N-halamine grafted PP to prepare antibacterial PP microfibers via sea-island spinning method (Fig. 12a) . The methacrylamide (MAM), N-tertbutyl acrylamide (NTBA), and 2,4-diamino-6-diallylamino-1,3,5-triazine (NDAM) were selected as functional N-halamine monomers to copolymerize with PP (Fig. 12b) .The grafted polymers were extruded with cellulose acetate butyrate (CAB), and then immersed in acetone to remove CAB. After that the grafted PP microfibers were fabricated in the form of continuous yarn comprising fibers with different average diameter of 6 μm and 0.6 μm, respectively. Among them, NDAM grafted PP (PP-g-NDAM) fibers with diameter of 0.6 μm showed maximum active chloride content due to the amount of the grafted monomers in PP and the higher surface areas of finer fibers (Fig. 12c-d) ,

thus endowing the PP-g-NDAM fibers with excellent bactericidal properties against E. coli (Fig. 12e) . Ref. [131] . Copyright 2008 Wiley.

Besides the above-mentioned spinning methods, others like dry-jet wet spinning and wet pinning, have also been used to fabricate NFMs. For example, Kocer et al. [132] reported N-halamine composite fibers of cellulose, starch, and an oligomeric hindered amine light stabilizer (HALS) by dry-jet wet spinning method. The cotton, freeze-dried starch, and HALS were dissolved in a certain ionic liquid, then the solutions were extruded and soaked in a tap water coagulation bath to obtain the composite fibers ( Fig. 13a-b) . After chlorination, the resulting N-halamine composite fibers were exposed to UV light and chlorinated repeatedly. As shown in Fig. 13c , over 70% chlorine loadings of the samples had been remained after 6 cyclic testing, indicating that the N-halamine fibers exhibited durable UV resistance and rechargeable chlorination properties.

J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f coli, respectively (Fig. 13f) .

Combining the unique advantages of structural continuity of fibrous materials with rechargeable bactericidal activity of N-halamines, the NFMs have attracted increasing attention in the past few decades and shown great potentials in different fields. This section will concentrate on the recent advances in the functional applications of NFMs, involving bioprotective clothing, water disinfection, air purification, and biomedicine.

Bioprotective clothing is dispensable for healthcare workers to prevent the pathogenic microbial transmission in the workplace. Current bioprotective clothing can effectively intercept the pathogens physically, but the sustained infection activity of pathogens could easily cause cross-contamination and postinfection [134] . Moreover, in order to make sure the thorough interception of pathogens, the clothing is usually subjected to poor breathability, undoubtably posing a huge burden for the healthcare workers. Nowadays, the development of NFMs provides an alternative way to fabricate bioprotective clothing that can not only inactivate the pathogenic bacteria but also possess good wearing comfort.

For example, Zhu et al. [42] reported composite membranes with poly(vinyl alcohol-co-ethylene-g-diallylmelamine) (PVA-co-PE-g-DAM) nanofibers layered on poly(propylene-g-diallylmelamine) (PP-g-DAM) meltblown nonwoven fabrics, which could be used for bioprotective clothing materials. The PVA-co-PE-g-DAM nanofibers, which was fabricated by sea-island spinning method, formed a J o u r n a l P r e -p r o o f nanoweb-like structure on the meltblown fabrics with tunable pore size (Fig. 14a) . After being exposed to dilute bleach, the N-halamine precursor moieties would be transformed into active antibacterial N-halamine structures, achieving a complete kill of E. coli within 15 min (Fig. 14b) . Besides, the wearing comfort performance of the composite membranes was evaluated by measuring air permeability and water vapor transmission. As shown in Fig. 14c Chemical Society.

Pathogenic microbial contamination in natural and drinking water constitutes a major threat of human health and global economies [136, 137] . Disinfecting water in an efficient, reliable, and sustainable manner is a huge challenge that public health confronts today. The most popular methods of water disinfection are the addition of halogen-based disinfectants, such as free chlorine and other analogues, which could effectively address the problems of microbial-containing water with quality and supply. However, these treatment methods come with the drawbacks of infrastructure-dependent disinfection systems and irreversible decrease in biocidal activity caused by the consumption of disinfectants [138] . Interestingly, N-halamine fibrous materials have received great attention for water disinfection due to its high biocidal efficacy, low toxicity, and simple rechargeability. As a typical example, Si et al. [135] presented renewable bactericidal nanofibrous membranes by covalently incorporating N-halamine moieties into electrospun nanofibers, which could effectively disinfect contaminated water by filtration (Fig. 14d) . The polymeric (Fig. 14f) .

To address the problems of specialization, high cost, and time consuming of electrospun water disinfection membranes, Kim et al. [75] developed a cellulose filter using only water as solvent, achieving the energy-saving and improved productivity for water disinfection application. The BTCA/m-phenylenediamine N-halamine modification solution was attached on cellulose filter by pad-dry-curing method. The water disinfection process was employed by non-pressure-driven filtration using Buchner funnel. The bacterial solution was added to the treated cellulose filter that placed on the funnel, and the filtrate was plated on the agar for further bacterial enumeration. As a result, it was found that the chlorinated filters could completely inactivate bacteria in water within an actual contact time of 15.9 s.

The fatal danger of airborne microorganism and particulate pollution on health promotes the development of air purification materials [139] . Antibacterial air purification materials play a crucial role in the daily protection of human health, especially for the airborne microbial transmitted diseases. Recently, Wang et al. [125] fabricated bactericidal polysulfonamide (PSA) nanofibrous membranes by combining electrospinning method with Lewis acid-assisted chlorination, holding great promise J o u r n a l P r e -p r o o f as a functional layer for purifying contaminated air. PSA which had abundant amide groups was electrospun into nanofibrous membranes as the N-halamine precursor.

After the creative Lewis acid-assisted chlorination treatment, the membranes were covered on the 3M surgical mask as a filtration and bactericidal layer to evaluate their air purification performance (Fig. 15a) . As exhibited in Fig. 15b , no bacterial colonies could be observed on the surface of the membranes and the covered area, showing excellent biocidal activity when compared with the control area. Additionally, the membranes also exhibited high filtration efficiency (99.8%) towards the aerosol particles with a diameter of 0.3-0.5 μm, demonstrating exceptional filtration performance with low basis weight (Fig. 15c) . 

The misery from wound and the possible microbial-related infection afflicted considerable patients. Wound dressing would be an effective barrier against environment contaminants, which plays a promising role in protecting wound physically and promoting wound healing [142] . Benefitting from the bactericidal J o u r n a l P r e -p r o o f function and good air permeability, the NFMs have been used as wound dressing materials recently. For instance, Gao et al. [141] constructed a N-halamine modified antibacterial cotton fabric, which could be used as wound dressing materials for anti-infective wound therapy (Fig. 15d ). They first prepared N-halamine polymer based on the copolymerization of methyl methacrylate (MMA) and ADMH. Then the N-halamine polymer nanomaterials were loaded on the cotton substrate by negative pressure suction filtration technique. The resulting materials could almost inactivate the E. coli and S. aureus with survival percentages of 0% and 12.38% within 60 min, respectively (Fig. 15e) . Moreover, the wound therapy ability of the materials has been evaluated towards the wounds of normal mice. Compared with the control and the unchlorinated polymers, the N-halamine polymer could effectively reduce the wound size by 55.09 ± 1.56%, demonstrating the effectiveness of the N-halamines for wound therapy.

Through years of continued efforts, impressive achievements have been engaged in the development of N-halamine compounds and the resultant N-halamine materials, as well as the antibacterial behavior of N-halamines. Antibacterial NFMs have been studied increasingly during the past years owing to the structural continuity, effectiveness toward a broad spectrum of microorganisms, renewable antibacterial activity, and low toxicity. Up to now, various NFMs were fabricated through surface modification method and one-step spinning. Surface modification is a method that grafting or coating N-halamines onto the available fibrous materials, which can be Accordingly, more facile preparation methods that are suitable for industrial production should be developed.

Although much challenging work is still in front of use for the fabrication of next-generation NFMs. We believe that the endless efforts devoted to the exploration of NFMs will finally overcome the above-mentioned obstructions and push forward their rapid development. It is expected that the summarized N-halamine compounds, antibacterial behavior, fabrication strategies and functional applications of NFMs, combining with the well-selected references and some personal opinions, can provide some guidance and suggestions to the researchers in related fields.

Universities (CUSF-DH-D-2018025).

The authors declare that they have no competing interests.

COVID-19) pandemic

COVID-19 in persons with haematological cancers

Antibacterial coatings: challenges, perspectives, and opportunities

Dual-function antibacterial surfaces for biomedical applications

Antibacterial surfaces: the quest for a new generation of biomaterials

Antibacterial activity of silver nanoparticles: a surface science insight

Silver as antibacterial agent: ion, nanoparticle, and metal

Emergence of resistance to antibacterial agents: the role of quaternary ammonium compounds-a critical review

Quaternary ammonium compounds: an antimicrobial mainstay and platform for innovation to address bacterial resistance

Recent developments in antibacterial and antifungal chitosan and its derivatives

Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance

Chemical insights into antibacterial N-halamines

Chemistry of N-bromamines and N-chloramines

Syntheses and antibacterial activity of new N-halamine compounds

The stabilities of new N-halamine water disinfectants

Disinfecting water with a mixture of free chlorine and an organic N-halamine

Antibacterial surface design-contact kill

Durable and regenerable antibacterial finishing of fabrics: biocidal properties

Polymeric antimicrobial N-halamine epoxides

Killing mechanism of stable N-halamine cross-linked polymethacrylamide nanoparticles that selectively target bacteria

N-bromo-hydantoin grafted polystyrene beads: synthesis and nano-micro beads characteristics for achieving controlled release of active oxidative bromine and extended microbial inactivation efficiency

Efficacy of N-halamine compound on reduction of microorganisms in absorbent food pads of raw beef

Durable and regenerable antimicrobial textiles: Synthesis and applications of 3-methylol-2,2,5,5-tetramethylimidazolidin-4-one (MTMIO)

Antimicrobial N-halamine polymers and coatings: a review of their synthesis, characterization, and applications

Combined halogen disinfectants in poultry-processing

Novel N-halamine disinfectant compounds

Kinetic versus thermodynamic control in chlorination of imidazolidin-4-one derivatives

Antimicrobial activity of N-chloramine compounds

Antimicrobial activities of N-chloramines and diazolidinyl urea

N-halo derivatives V: comparative antimicrobial activity of soft N-chloramine systems

Preparation of novel biocidal N-halamine polymers

A novel biocidal styrenetriazinedione polymer

Durable antimicrobial cotton fabrics treated with a novel N-halamine compound

N-halamine modified polyester fabrics: preparation and biocidal functions

Disinfection of water by N-halamine biocidal polymers

Performance of a new polymeric water disinfectant

Antimicrobial treatment of nylon

A new cyclic N-halamine biocidal polymer

Preparation of biocidal 4-ethyl-4-(hydroxymethyl)oxazolidin-2-one-based N-halamine polysiloxane for impregnation of polypropylene in supercritical CO 2

Preparation and characterization of PHB/PBAT-based biodegradable antibacterial hydrophobic nanofibrous membranes

Chemical and biological decontamination functions of nanofibrous membranes

Durable and regenerable biocidal polymers: acyclic N-halamine cotton cellulose

Functional modification of poly(ethylene terephthalate) with an allyl monomer: chemistry and structure characterization

Unexpected enhancement in antibacterial activity of N-halamine polymers from spheres to fibers

Novel refreshable N-halamine polymeric biocides: N-chlorination of aromatic polyamides

Antimicrobial Polyethylene terephthalate (PET) treated with an aromatic N-halamine precursor, m-Aramid

Engineering an antibacterial nanofibrous membrane containing N-halamine for recyclable wound dressing application

Electrospun polyacrylonitrile nanofibrous biomaterials

Novel N-Br bond-containing N-halamine nanofibers with antibacterial activities

Optimizing halogenation conditions of N-halamine polymers and investigating mode of bactericidal action

N-halamine-containing electrospun fibers kill bacteria via a contact/release co-determined antibacterial pathway

Biocidal efficacy, biofilm-controlling function, and controlled release effect of chloromelamine-based bioresponsive fibrous materials

Synthesis, characterization, and antibacterial activities of novel N-halamine polymer beads prepared by suspension copolymerization

Biocidal poly(styrenehydantoin) beads for disinfection of water

Immobilization of cyclic N-halamine on polystyrene-functionalized silica nanoparticles: synthesis, characterization, and biocidal activity

Modifying Fe 3 O 4 -functionalized nanoparticles with N-halamine and their magnetic/antibacterial properties

Functionalizing PS microspheres by supercritical deposition of P(S-b-tBA) for diverse interfacial properties exemplified with biocidal ability

Characterization and antibacterial properties of N-halamine-derivatized cross-linked polymethacrylamide nanoparticles

Barbituric acid-based magnetic N-halamine nanoparticles as recyclable antibacterial agents

Polymerization of a hydantoinylsiloxane on particles of silicon dioxide to produce a biocidal sand

Development of an antimicrobial microporous polyurethane membrane

Amine, melamine, and amide N-halamines as antimicrobial additives for polymers

Electrochemical treatments using tin oxide anode to prevent biofouling

Poly(vinyl alcohol) blend film with m-Aramid as an N-halamine precursor for antimicrobial activity

Self-healing antimicrobial polymer coating with efficacy in the presence of organic matter

Antibiofilm effect of poly(vinyl alcohol-co-ethylene) halamine film against listeria innocua and escherichia coli O157:H7

N-halamine modified thermoplastic polyurethane with rechargeable antimicrobial function for food contact surface

Mechanically robust and transparent N-halamine grafted PVA-co-PE films with renewable antimicrobial activity

Rechargeable antibacterial N-halamine films with antifouling function for food packaging applications

Durable and regenerable antibacterial finishing of fabrics with a new hydantoin derivative

Decorating CdTe QD-embedded mesoporous silica nanospheres with Ag NPs to prevent bacteria invasion for enhanced anticounterfeit applications

An N-halamine-based rechargeable antimicrobial and biofilm controlling polyurethane

Preparation, characterization, and antibacterial activities of quaternarized N-halamine-grafted cellulose fibers

Water disinfection activity of cellulose filters treated with polycarboxylic acid and aromatic amine

Thermoplastic semi-IPN of polypropylene (PP) and polymeric N-halamine for efficient and durable antibacterial activity

Dual antibacterial functional regenerated cellulose fibers

Preparation and characterization of polymerizable hindered amine-based antimicrobial fibrous materials

Synthesis of an N-halamine monomer and its application in antimicrobial cellulose via an electron beam irradiation process

Biocidal activity of N-halamine methylenebisacrylamide grafted cotton

Novel refreshable N-halamine polymeric biocides containing imidazolidin-4-one derivatives

Self-assembled antibacterial coating by N-halamine polyelectrolytes on a cellulose substrate

Preparation of antimicrobial and hemostatic cotton with modified mesoporous particles for biomedical applications

N-halamine incorporated antimicrobial nonwoven fabrics for use against avian influenza virus

N-halamine-modified polyglycolide (PGA) multifilament as a potential bactericidal surgical suture: in vitro study

Rechargeable antimicrobial coatings for poly(lactic acid) nonwoven fabrics

Synthesis of polysiloxane with quaternized N-halamine moieties for antibacterial coating of polypropylene via supercritical impregnation technique

Interpenetration of polyethylene terephthalate with biocidal quaternary ammonium/N-chloramine polysiloxane in supercritical CO 2

Cytocompatible and regenerable antimicrobial cellulose modified by N-halamine triazine ring

Biodegradable polyhydroxybutyrate/poly-epsilon-caprolactone fibrous membranes modified by silica composite hydrol for super hydrophobic and outstanding antibacterial application

Multi-functional properties of cotton fabrics treated with UV absorber and N-halamine, Fibers Polym

Biocompatible antimicrobial cotton modified with tricarbimide-based N-halamine

Rechargeable biocidal cellulose: synthesis and application of 3-(2,3-dihydroxypropyl)-5,5-dimethylimidazolidine-2,4-dione

N-halamine-coated cotton for antimicrobial and detoxification applications

Antimicrobial fibers created via polycarboxylic acid durable press finishing

Improved UV stability of antibacterial coatings with N-halamine/TiO 2

Studies of PET nonwovens modified by novel antimicrobials configured with both N-halamine and dual quaternary ammonium with different alkyl chain length

In situ green synthesis of rechargeable antibacterial N-halamine grafted poly(vinyl alcohol) nanofibrous membranes for food packaging applications

Durable and regenerable antimicrobial textiles: thermal stability of halamine structures

Preparation and characterization of chlorinated cross-linked chitosan/cotton knit for biomedical applications

N-halamine-bonded cotton fabric with antimicrobial and easy-care properties

The chemistry and applications of antimicrobial polymers: a state-of-the-art review

Acyclic N-halamine-based fibrous materials: preparation, characterization, and biocidal functions

Acyclic halamine polypropylene polymer: effect of monomer structure on grafting efficiency, stability and biocidal activities

Preparation of rechargeable biocidal polypropylene by reactive extrusion with diallylamino triazine

Functional modification of poly(ethylene terephthalate) with an allyl monomer: chemistry and structure characterization

Dual action bactericides: quaternary ammonium/N-halamine-functionalized cellulose fiber

Antibacterial functionalization of cotton fabrics by electric-beam irradiation

High flame retardancy of oxidized polyacrylonitrile fibers prepared by effective plasma-assisted thermal stabilization and electron-beam irradiation

Advanced sorbents for oil-spill cleanup: recent advances and future perspectives

Gas sensors based on nano/microstructured organic field-effect transistors

Fabrication of cotton fabrics through in-situ reduction of polymeric N-halamine modified graphene oxide with enhanced ultraviolet-blocking, self-cleaning, and highly efficient, and monitorable antibacterial properties

N-halamine biocidal coatings via a layer-by-layer assembly technique

Antimicrobial surface coatings for polypropylene nonwoven fabrics

Preparation and characterization of antimicrobial cotton fabrics via N-halamine chitosan derivative/poly(2-acrylamide-2-methylpropane sulfonic acid sodium salt) self-assembled composite films

Waterproof and breathable electrospun nanofibrous membranes

Synthesis of polysiloxane with 5,5-dimethylhydantoin-based N-halamine pendants for biocidal functionalization of polyethylene by supercritical impregnation

Biocidal nanofibers via electrospinning

Preparation and antimicrobial activity of beta-cyclodextrin derivative copolymers/cellulose acetate nanofibers

Development of cytocompatible antibacterial electro-spun nanofibrous composites

Electrospun composite nanofiber fabrics containing uniformly dispersed antimicrobial agents as an innovative type of polymeric materials with superior antimicrobial efficacy

Fabrication and evaluation of electrospun nanofibrous antimicrobial nylon 6 membranes

Antimicrobial m-Aramid nanofibrous membrane for nonpressure driven filtration

Novel inorganic-based N-halamine nanofibrous membranes as highly effective antibacterial agent for water disinfection

Rechargeable antibacterial polysulfonamide-based N-halamine nanofibrous membranes for bioprotective applications

Rechargeable polyamide-based N-halamine nanofibrous membranes for renewable, high efficiency, and antibacterial respirators

Poly(ADMH-MMA-HEMA) novel antibacterial fibers of amphiphilic N halamine polymer prepared by electrospinning

Poly(ethylene terephthalate) nanofibers made by sea-island-type conjugated melt spinning and laser-heated flow drawing

Fabrication and properties of poly(tetrafluoroethylene) nanofibres via sea-island spinning

Hierarchical polyamide 6 (PA 6) nanofibrous membrane with desired thickness as separator for high-performance lithium-ion batteries

Durable and rechargeable biocidal polypropylene polymers and fibers prepared by using reactive extrusion

Cellulose/starch/HALS composite fibers extruded from an ionic liquid

Novel PVDF hollow fiber ultrafiltration membranes with antibacterial and antifouling properties by embedding N-halamine functionalized multi-walled carbon nanotubes (MWNTs)

Daylight-driven rechargeable antibacterial and antiviral nanofibrous membranes for bioprotective applications

Biocidal and rechargeable N-halamine nanofibrous membranes for highly efficient water disinfection

The role of nanotechnology in tackling global water challenges

Biomimetic and superelastic silica nanofibrous aerogels with rechargeable bactericidal function for antifouling water disinfection

Science and technology for water purification in the coming decades

Metal-organic frameworks with photocatalytic bactericidal activity for integrated air cleaning

N-halamine functionalized electrospun poly(vinyl alcohol-co-ethylene) nanofibrous membranes with rechargeable antibacterial activity for bioprotective applications

Construction of antibacterial N-halamine polymer nanomaterials capable of bacterial membrane disruption for efficient anti-infective wound therapy

Electrofabrication of functional materials: chloramine-based antimicrobial film for infectious wound treatment

PHB/PCL electrospun membranes Hydantoin-containing N-halamines 99

Viscose fabrics Polysaccharide-containing N-halamines 99

Cotton/PET/Nylon-66/PP fabrics Hydantoin-containing N-halamines 99

Cotton fabrics Hydantoin-containing N-halamines 99

Design and fabrication strategies of N-halamine fibrous materials based on surface modification and one-step spinning are systematically reviewed

The functional applications of the N-halamine fibrous materials are discussed

Challenges and future research directions of the antibacterial N-halamine fibrous materials are provided

This work was supported by the National Natural Science Foundation of China (Nos. 

J o u r n a l P r e -p r o o f

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:J o u r n a l P r e -p r o o f